Leicester's virtual clinical trials revolutionize the way new drugs are developed

New cutting-edge research undertaken at the University of Leicester could revolutionize the way new drugs are developed and the way patients are cared for, through a pioneering new approach using virtual clinical trials.

Following a £500,000 Royal Academy of Engineering research funding award, Dr. Himanshu Kaul will expand research with his 'virtual asthma patient' to participate in virtual clinical trials, which could help make more accurate and timely predictions around which new drugs are successful and can offer benefits to patients.

Virtual clinical trials could also help doctors gain a better understanding of individual patient's disease progression, allowing them to tailor therapies to patients' individual needs and improve outcomes in a wider range of cases.

Currently, medications must meet a number of robust milestones over several years before human trials may begin, meaning that potentially life-saving drugs are often years away from patient use.

Dr. Kaul, Royal Academy of Engineering Research Fellow, said: "In a nutshell, more than 90% of drugs fail to reach the market. This is because we lack the capacity to predict the impact of drugs at the systems level, and this comes at a huge cost to pharmaceutical companies.

"In contrast, when aeronautical companies design a new plane, they run their design through rigorous mathematical models to predict how well the design will perform and optimize performance.

"There is no practical equivalent of this in the pharma industry, which will significantly drop the costs. My long-term research vision is to create software that will allow clinicians and pharmaceutical companies to predict how well a drug will perform in patients and offer a way to optimize its therapeutic efficacy."

Using agent-based modeling, Dr Kaul is collaborating with experts from the University of Leicester's Schools of Engineering and Mathematics and Department of Respiratory Sciences on his pioneering research project, titled 'The Lung Pharmacome'.

The project aims to produce working in silico lung by 2024, with the ambition of conducting patient-specific virtual clinical trials' by 2025 at the earliest. The initial area of focus for the research will be lung diseases, specifically asthma and chronic obstructive pulmonary disease (COPD), with scientists and clinicians at the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre's respiratory theme, based at Glenfield Hospital.

Dr. Kaul continued: "Lung diseases are a major source of socio-economic burden globally. In the UK alone, lung diseases are the third-worst killers, affecting one in five people, and responsible for a death, on average, every five minutes.

"Outside of that, the cost to the economy given a number of missed workdays and inpatient bed days is £11billion a year."

And identifying the right environment for his Fellowship was important to Dr. Kaul, who added: "The University of Leicester was an obvious choice as the institution to carry out this research vision due to its strong clinical expertise, the synergy between engineering and healthcare outcomes, and a focus on precision medicine.

"Its clinical partners make it an exceptionally strong science complex with research efforts in engineering and biomedical sciences that extend from the molecular to the clinical scale.

Duke's Mattingly presents 2021 SIAM Block Community Lecture at AN21 online

Jonathan Christopher Mattingly of Duke University has been selected to deliver the 2021 I.E. Block Community Lecture. He will be presenting the lecture at the SIAM Annual Meeting (AN21) which will be taking place virtually July 19 -23, 2021. Dr. Mattingly has been a proud and engaged member of SIAM for years. “SIAM was central to my scientific formation as an applied (stochastic) dynamicist,” Mattingly says. “I gave some of my first talks at SIAM Conferences and have been a regular at the SIAM Conference on Applications of Dynamical System for years as well as regularly attending many others. I feel strongly that the application of mathematics is important to our society and that the best applications breed great mathematics.” Jonathan Christopher Mattingly of Duke University

Dr. Mattingly grew up in Charlotte, North Carolina. He graduated from the NC School of Science and Mathematics and received a B.S. is Applied Mathematics with a concentration in physics from Yale University. After two years abroad with a year spent at ENS Lyon studying nonlinear and statistical physics on a Rotary Fellowship, he returned to the U.S. to attend Princeton University where he obtained a Ph.D. in Applied and Computational Mathematics in 1998 under the supervision of Yakov Sinai. After four years as a Szegö assistant professor at Stanford University and one year as a member of the IAS in Princeton, he moved to Duke in 2003, where he is currently James B. Duke Professor of Mathematics and a Professor of Statistical Science.

Since 2013 he has also been working to understand and quantify gerrymandering and its interaction with a region's geopolitical landscape. This has led him to testify in several court cases including Common Cause v. Rucho, which went all the way to the U.S. Supreme Court. He was also involved with a sequence of North Carolina state court cases which led to the NC congressional and both NC legislative maps being deemed unconstitutional and replaced for the 2020 elections. He was awarded the Defender of Freedom award by the Common Cause for his work on Quantifying Gerrymandering.

More info about the 2021 I. E. Block Community Lecture will be available in the coming months, but Dr. Mattingly gave us a preview of his work in gerrymandering that will be presented: The group at Duke has been centered on understanding and quantifying gerrymandering. The interaction between our laws and the geopolitical structure of our states is complicated enough that it resists simple reductive principles as a means of analysis. We have used computational sampling methods to create normative ensembles of maps that can be used as a baseline against which other maps can be compared. Central to this work has been a dialogue between lawyers and policy advocates and mathematicians. There are challenges in how to formulate the policy questions mathematically, in how to perform the needed collations in a computationally feasible way, and then in how to best transmit the results to empower policymakers, the courts, and the polis at large by increasing their understanding of the issues in play.

“It is important for people to understand gerrymandering and its effect on our election system,” he says. “My hope is to give a framework so that everyone can formulate the central issues in gerrymandering and be empowered to enter into the conversation both in the classroom and our political forums.”Dr. Mattingly is the recipient of an NSF CAREER award, a Presidential Early Career Award for Scientists and Engineers (PECASE), and a Sloan Foundation Faculty Fellowship. He is a fellow of the Institute for Mathematical Statistics (IMS) and the American Mathematics Society (AMS) and has served on the advisory boards for several NSF institutes. The I. E. Block Community Lecture is given each year at the SIAM Annual Meeting and is free and open to the public. Due to COVID-19, SIAM AN21 and the 2021 Block Lecture are happening virtually; the date and time will be announced in April.

Japanese simulation method predicts the performance of methane conversion solid catalyst

Japanese researchers performed supercomputation of reaction kinetic information from first-principles calculations based on quantum mechanics, and developed methods and programs to carry out kinetic simulations without using experimental kinetic results. This method is expected to accelerate the search for various materials to achieve a carbon-free society.

Japanese researchers have developed a simulation method to theoretically estimate the performance of heterogeneous catalysts by combining first-principles calculation and kinetic calculation techniques. Up to now, simulation studies mainly focused on a single or limited number of reaction pathways, and it was difficult to estimate the efficiency of a catalytic reaction without experimental information.

Figure 1. Mole fraction changeMole fraction along the reaction time (s) calculated by the reactor simulation. The inlet gas consisted of CH4, O2, and He (as inert gas). The total pressure was set to P = 1 bar, and the partial pressure ratio of CH4, O2, and He was set to 2:1:4. The volumetric flow rate was set to 1 mL/s, and the reaction temperature was 700 °C. The catalyst weight was 1 g. ©Atsushi Ishikawa

Atsushi Ishikawa, Senior Researcher, Center for Green Research on Energy and Environmental Materials, National Institute for Materials Science (NIMS), performed computation of reaction kinetic information from first-principles calculations based on quantum mechanics, and developed methods and programs to carry out kinetic simulations without using experimental kinetic results. Then he applied the findings to the oxidative coupling of methane (OCM) reaction, which is an important process in the use of natural gas. He could successfully predict the yield of the products, such as ethane, without experimental information on the reaction kinetics. He also predicted changes in yield depending on the temperature and partial pressure, and the results reproduced faithfully the existing experimental results.

This research shows that the supercomputer simulation enables the forecasting of the conversion of reactants and the selectivity of products, even if experimental data are unavailable. The search for catalytic materials led by theory and calculation is expected to speed up. Furthermore, this method is highly versatile and can be applied not only to methane conversion catalysts but also to other catalyst systems such as automobile exhaust gas purification, carbon dioxide reduction, and hydrogen generation, and is expected to contribute to the realization of a carbon-free society. Figure 2. Concept of the studyGraphical concept figure showing the combined approach of first-principle calculation and microkinetics. Catalytic activities such as conversion and selectivity are predicted. The catalytic reaction network is also obtained thus detailed analysis on the catalyst reaction is possible. ©Atsushi Ishikawa